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7-ketocholesterol induces apoptosis in differentiated PC12 cells via reactive oxygen species-dependent activation of NF-κB and Akt pathways.
Neurochem Int. 2011 Jan; 58(1):52-9.NI

Abstract

Cholesterol oxidation products formed under the enhanced oxidative stress in the brain are suggested to induce neuronal cell death. However, it is still unknown whether oxysterol-induced apoptosis in neuronal cells is mediated by Akt and NF-κB pathways. We assessed the apoptotic effect of 7-ketocholesterol against differentiated PC12 cells in relation to activation of the reactive oxygen species-dependent nuclear factor (NF)-κB, which is mediated by the Akt pathway. 7-Ketocholesterol induced a decrease in cytosolic Bid and Bcl-2 levels, increase in cytosolic Bax levels, cytochrome c release, caspase-3 activation and upregulation of p53. 7-Ketocholesterol induced an increase in phosphorylated inhibitory κB-α, NF-κB p65 and NF-κB p50 levels, binding of NF-κB p65 to DNA, and activation of Akt. Treatment with Bay 11-7085 (an inhibitor of NF-κB activation) and oxidant scavengers, including N-acetylcysteine, prevented the 7-ketocholesterol-induced formation of reactive oxygen species, activation of NF-κB, Akt and apoptosis-related proteins, and cell death. Results from this study suggest that 7-ketocholesterol may exert an apoptotic effect against PC12 cells by inducing activation of the caspase-8-dependent pathway as well as activation of the mitochondria-mediated cell death pathway, leading to activation of caspases, via the reactive oxygen species-dependent activation of NF-κB, which is mediated by the Akt pathway.

Authors+Show Affiliations

Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, South Korea.No affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

21035514

Citation

Jang, Eun-Ra, and Chung Soo Lee. "7-ketocholesterol Induces Apoptosis in Differentiated PC12 Cells Via Reactive Oxygen Species-dependent Activation of NF-κB and Akt Pathways." Neurochemistry International, vol. 58, no. 1, 2011, pp. 52-9.
Jang ER, Lee CS. 7-ketocholesterol induces apoptosis in differentiated PC12 cells via reactive oxygen species-dependent activation of NF-κB and Akt pathways. Neurochem Int. 2011;58(1):52-9.
Jang, E. R., & Lee, C. S. (2011). 7-ketocholesterol induces apoptosis in differentiated PC12 cells via reactive oxygen species-dependent activation of NF-κB and Akt pathways. Neurochemistry International, 58(1), 52-9. https://doi.org/10.1016/j.neuint.2010.10.012
Jang ER, Lee CS. 7-ketocholesterol Induces Apoptosis in Differentiated PC12 Cells Via Reactive Oxygen Species-dependent Activation of NF-κB and Akt Pathways. Neurochem Int. 2011;58(1):52-9. PubMed PMID: 21035514.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 7-ketocholesterol induces apoptosis in differentiated PC12 cells via reactive oxygen species-dependent activation of NF-κB and Akt pathways. AU - Jang,Eun-Ra, AU - Lee,Chung Soo, Y1 - 2010/10/28/ PY - 2010/09/01/received PY - 2010/10/20/revised PY - 2010/10/21/accepted PY - 2010/11/2/entrez PY - 2010/11/3/pubmed PY - 2011/4/1/medline SP - 52 EP - 9 JF - Neurochemistry international JO - Neurochem. Int. VL - 58 IS - 1 N2 - Cholesterol oxidation products formed under the enhanced oxidative stress in the brain are suggested to induce neuronal cell death. However, it is still unknown whether oxysterol-induced apoptosis in neuronal cells is mediated by Akt and NF-κB pathways. We assessed the apoptotic effect of 7-ketocholesterol against differentiated PC12 cells in relation to activation of the reactive oxygen species-dependent nuclear factor (NF)-κB, which is mediated by the Akt pathway. 7-Ketocholesterol induced a decrease in cytosolic Bid and Bcl-2 levels, increase in cytosolic Bax levels, cytochrome c release, caspase-3 activation and upregulation of p53. 7-Ketocholesterol induced an increase in phosphorylated inhibitory κB-α, NF-κB p65 and NF-κB p50 levels, binding of NF-κB p65 to DNA, and activation of Akt. Treatment with Bay 11-7085 (an inhibitor of NF-κB activation) and oxidant scavengers, including N-acetylcysteine, prevented the 7-ketocholesterol-induced formation of reactive oxygen species, activation of NF-κB, Akt and apoptosis-related proteins, and cell death. Results from this study suggest that 7-ketocholesterol may exert an apoptotic effect against PC12 cells by inducing activation of the caspase-8-dependent pathway as well as activation of the mitochondria-mediated cell death pathway, leading to activation of caspases, via the reactive oxygen species-dependent activation of NF-κB, which is mediated by the Akt pathway. SN - 1872-9754 UR - https://www.unboundmedicine.com/medline/citation/21035514/7_ketocholesterol_induces_apoptosis_in_differentiated_PC12_cells_via_reactive_oxygen_species_dependent_activation_of_NF_κB_and_Akt_pathways_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0197-0186(10)00325-6 DB - PRIME DP - Unbound Medicine ER -